title: Drug induced hepatotoxicity: data from the Serbian pharmacovigilance database.
abstract: OBJECTIVE
  The main aim of this study was to determine the most frequently reported drugs to the Serbian Pharmacovigilance Database (SPD) with suspected induced hepatotoxicity. Additionally, reasons for the low reporting rate of adverse drug reactions (ADRs) in Serbia were identified.
  
  
  METHODS
  Retrospective observational study of spontaneously reported ADRs recorded in the SPD from January 1995 to December 2008 was performed. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify cases of hepatobiliary disorders (HD). Drugs were classified using the Anatomical Therapeutic Chemical (ATC) classification. Medline and WHO-UMC databases were used to address specific queries suggested by our results. The questionnaire was used to investigate the health care professionals' knowledge and practice related to spontaneous reporting.
  
  
  RESULTS
  Among the 1804 reports of ADRs recorded in the SPD between 1995 and 2008, 70 (3.9%) cases of HD were identified. Drugs most frequently associated with hepatotoxicity were anti-infectives for systemic use, drugs affecting the nervous system, herbal products, hypolipemics, and anticoagulant drugs (26.83, 24.39, 12.20, 9.76, and 8.54% cases, respectively). Four cases (5.71%) of liver injury resulted in death, which accounted for 10.26% of all ADR fatalities reported to the SPD. The main reasons for not reporting ADRs were lack of reporting knowledge (30.26%), well-known ADRs (29.89%), and insecurity about causality relationship (15.50%).
  
  
  CONCLUSIONS
  Anti-infectives, nervous system drugs, and herbal products were the most common drug classes reported for hepatotoxicity in Serbia. There is a need for additional education about ADRs, and enhanced reporting by health care professionals.
authors.affiliation: Medicines and Medical Devices Agency of Serbia, Belgrade, Republic of Serbia.
authors.forename: Marija
authors.initials: M
authors.lastname: Petronijevic
authors.forename: Katarina
authors.initials: K
authors.lastname: Ilic
authors.forename: Ayako
authors.initials: A
authors.lastname: Suzuki
mesh_terms: D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D000368:Aged; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology* / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D016208:Databases, Factual; D005260:Female; D007722:Health Knowledge, Attitudes, Practice; D006281:Health Occupations / Q000706:statistics & numerical data; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D055771:Serbia / Q000453:epidemiology; D011795:Surveys and Questionnaires; D055815:Young Adult